Navegando por Palavras-chave "Receptors, muscarinic"

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    A diversidade estrutural de peptídeos potenciadores da bradicinina da Bothrops jararaca (Bj-BPPs) proporciona ações sinérgicas no sistema cardiovascular
    (Universidade Federal de São Paulo (UNIFESP), 2010-03-31) Morais, Kátia Luciano Pereira [UNIFESP]; Camargo, Antonio Carlos Martins de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Our laboratory has shown that one gene codes for the protein precursor that yields the natriuretic peptide type C (CNP) after having been processed, along with a variety of proline-rich peptides, known as bradykinin-potentiating peptides or BPPs. Showing little differences, this precursor is expressed in the venom gland and the neuroendocrine region of the Bothrops jararaca brain. All processing products have in common that they act on the cardiovascular system, lowering arterial blood pressure and heart frequency. This intriguing fact led us to question whether the different peptides display similar mechanisms of action. Surprisingly, the present study showed that the answer is negative, although we cannot, at the present time, explain in full detail how each peptide acts in the complex mechanism, responsible for vascular tonus and cardiac frequency. Historically, the demonstration that the Bradykinin-Potentiating Peptides from Bothrops jararaca (Bj-BPPs) were natural inhibitors of the angiotensin converting enzyme (ACE) had a wide medical impact. In fact, this inhibition seemed to fully explain the strong anti-hypertensive action of these peptides, therefore being employed as structural models for the development of a site-directed inhibitor, Captopril, a drug used worldwide for the treatment of systemic human arterial hypertension. Recent experimental evidences, however, suggest that the anti-hypertensive activity of the Bj-BPPs is not due exclusively to the inhibition of the ACE. Our group demonstrated that the antihypertensive action of Bj-BPP-10c, for instance, is due to the activation of L-arginine generation, which is essential for NO production, a potent vasodilator. Moreover, it also regulates the arterial baroreflex and intracellular calcium signaling, which contribute to NO production in endothelial and neuronal cells. In the present work we studied the mechanism of action of other Bj-BPPs found in the above mentioned precursor. We showed that the mechanism of action of Bj-BPP-5a involves bradykinin B2 receptor, the muscarinic receptor, subtype M1, and NO production. Bj-BPP-11e probably acts on a membrane receptor, thereby explaining its effects on cardiovascular parameters. The mechanism of action of Bj-BPP-12b might be explained by Bk potentiation and/or by ACE inhibition and Bj- BPP-13a action on by muscarinic receptor subtype M3 and the ASS. Interestingly, Bj-BPP-9a, which was the model molecule for the synthesis of Captopril, seems to act predominantly as a classic ACE inhibitor. Beside the pharmacological interest, our work also revealed, for the first time, that snake toxins also employ the well-known strategy in hormone-peptide generation, that is, they use the processing of a polyprotein to generate peptides which display a synergistic action.
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    Influência da aprendizagem e da manipulação do sistema colinérgico muscarínico na sensibilização ao efeito estimulante do etanol
    (Universidade Federal de São Paulo (UNIFESP), 2011-02-21) Takahashi, Shirley [UNIFESP]; Souza-Formigoni, Maria Lucia Oliveira de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Several authors suggest that behavioral sensitization, characterized as psychomotor activity increase in response to psychoactive drugs repeated administration, seems to play a fundamental role in the development of abuse and dependence, increasing the reinforcement property of these substances. Animals that develop sensitization to ethanol differ regarding the binding to some neurotransmitter receptors and also differ regarding the response to the administration of agonists and antagonists of these receptors. Behavioral sensitization is a complex phenomenon that involves different factors, being affected by environment and learning. To evaluate the influence of learning capacity in the sensitization process, in the present study we compared the performance of two groups of mice that presented different levels of sensitization (high and low) in two different learning tasks (appetitive and aversive). We also evaluated the influence of an amnestic drug (scopolamine) in the development and expression of sensitization. It was observed that mice with different levels of sensitization did not differ regarding their learning capacity after chronic treatment with ethanol, in both tasks. Scopolamine, when administered in the dorsal hippocampus simultaneously with ethanol treatment, did not alter the sensitization development. However, when administered subcutaneously it induced higher levels of locomotor activity in those animals that had already developed high sensitization than in low sensitized mice or in the control group. This phenomenon was not observed when scopolamine was administered directly in the nucleus accumbens. When administered in combination with ethanol, it blocked the sensitization. These data suggest that the cholinergic system acts as a neuromodulator in the sensitization process. However, the cholinergic system seems to act in different ways depending on the level of sensitization developed by the animal.
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    Influência do Sistema Colinérgico na sensibilização ao efeito estimulante do etanol
    (Universidade Federal de São Paulo (UNIFESP), 2006-01-01) Takahashi, Shirley [UNIFESP]; Souza-Formigoni, Maria Lucia Oliveira de [UNIFESP]; Oliveira, Maria Gabriela Menezes de; Quadros, Isabel Marian Hartmann de; Universidade Federal de São Paulo (UNIFESP)
    Various neurotransmission systems have influence on the behavioral sensitization process developed after repeated administration of some drugs of abuse, among them the cholinergic system, which modulates the dopaminergic pathway’s functioning. In this study we evaluated the influence of scopolamine (an antagonist of cholinergic muscarinic receptors) on the development and _expression of behavioral sensitization to ethanol (Study I), as well as on the M1 binding, in animals classified as presenting high (AS) or low (BS) sensitization to ethanol (Study II). In Study I, four groups of male Swiss albino mice received one of the following during 21 days: saline+saline (sal/sal); 1.0 mg/kg of scopolamine+saline (escop/sal); salina+2.2 g/kg of ethanol (sal/2.2EtOH) or 1.0 mg/kg scopolamine+2.2 g/kg of ethanol (escop/2.2EtOH). Their locomotor activity was recorded during 20 minutes on the first, 7th, 14th and 21st days of treatment. Acutely, neither ethanol nor scopolamine altered their locomotor activity; however the co-administration of the both drugs induced a significant depressor effect to which tolerance was developed. Only the sal/2.2EtOH group developed sensitization. After the treatment, 3 challenge tests were carried out (on days 28th, 31st and 34th), in which half of the sal/sal group received saline and the other half received the challenge drug (ethanol in challenges 1 and 2 and scopolamine in challenge 3). In challenges 1 and 3 the animals were tested in activity cages and only the sal/2.2EtOH and escop/2.2EtOH groups expressed sensitization, suggesting there is cross-sensitization between ethanol and scopolamine. In challenge 2, which was conducted in a new environment (open-field arena), the _expression of the sensitization was blocked. In Study II, mice were treated during 21 days with saline or 2.2 g/kg ethanol (i.p.) and the ethanol treated mice were classified as AS or BS, according to their locomotor activity on day 21st. The animals were sacrificed and the bindings to M1 sites were examined by auto-radiographic analyses. No significant differences were found among groups (AS, BS and control) in any of the 20 brain regions analyzed. The present results suggest that scopolamine influences the process of sensitization to ethanol and that the cholinergic system participates in this process. However, the neuroadaptation that occurred after chronic ethanol treatment does not seem to change the binding to M1.